In recent years a great deal of interest has been focused on the role of sodium and calcium in the pathogenesis of hypertension. Whereas the evidence linking sodium ingestion to the genesis of hypertension in both man and in experimental animals is sufficiently convincing, serious doubts still remain as to the role of abnormalities in calcium metabolism in the genesis of hypertension. The most current accepted hypothesis linking sodium intake to hypertension is that predisposed human subjects or animals have a genetic defect involving the ability of the kidneys to excrete a sodium load; this leads to sodium retention and to stimulation of humoral factors (natriuretic factors?) which are ultimately responsible for the development of hypertension. Ingestion of high sodium intake is not a condition sine qua non for the development of hypertension in spontaneously hypertensive rats (SHR), but it aggravates hypertension through stimulation of the sympathetic nervous system. The mechanisms linking abnormalities in calcium metabolism to the genesis and development of hypertension remain unclear. Moreover, the mechanisms of the hypotensive effect of increased dietary calcium intake in SHR are not elucidated. It is possible that calcium may affect sympathetic nervous system activity and consequently, blood pressure. The hypothesis to be tested in this research proposal are that the abnormality in sodium metabolism in experimentally hypertensive rats is secondary to hyperactivity of the sympathetic nervous system (SNS) and that alterations in calcium balance may affect blood pressure through action on SNS. To test these hypothesis the following series of experiments are planned in SHR using WKY rats as controls: 1) studies on the effect of SNS stimulation on renal nerve activity and renal sodium handling in pre-hypertensive SHR; 2) effect of sympathetic nerve inhibition on renal sodium handling in pre-hypertensive SHR; 3) studies to determine whether abnormalities in calcium metabolism precede or follow the development of hypertension and whether increased dietary calcium lowers blood pressure through inhibition of SNS.